Ameliorative effects of elderberry (Sambucus nigra L.) extract and extract-derived monosaccharide-amino acid on H2O2-induced decrease in testosterone-deficiency syndrome in a TM3 Leydig cell

PLoS One. 2024 Apr 25;19(4):e0302403. doi: 10.1371/journal.pone.0302403. eCollection 2024.

Abstract

With aging, men develop testosterone-deficiency syndrome (TDS). The development is closely associated with age-related mitochondrial dysfunction of Leydig cell and oxidative stress-induced reactive oxygen species (ROS). Testosterone-replacement therapy (TRT) is used to improve the symptoms of TDS. However, due to its various side effects, research on functional ingredients derived from natural products that do not have side effects is urgently needed. In this study, using the mitochondrial dysfunction TM3 (mouse Leydig) cells, in which testosterone biosynthesis is reduced by H2O2, we evaluated the effects of elderberry extract and monosaccharide-amino acid (fructose-leucine; FL) on mRNA and protein levels related to steroidogenesis-related enzymes steroidogenic acute regulatory protein (StAR), cytochrome P450 11A1(CYP11A1, cytochrome P450 17A1(CYP17A1), cytochrome P450 19A1(CYP19A1, aromatase), 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β-hydroxysteroid dehydrogenase(17β-HSD). We analyzed elderberry extract and extract-derived FL for changes in ROS scavenging activity and testosterone secretion. Elderberry extract and FL significantly reduced H2O2-induced intracellular ROS levels, improved testosterone secretion, and increased the mRNA and protein expression levels of steroidogenesis-related enzymes (StAR, 3b-HSD, 17b-HSD, CYP11A1, CYp17A1). However, the conversion of testosterone to estradiol was inhibited by elderberry extract and extract-derived FL, which reduced the mRNA and protein expression of CYP19A1. In conclusion, elderberry extract and FL are predicted to have value as novel functional ingredients that may contribute to the prevention of TDS by ameliorating reduced steroidogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Cell Line
  • Hydrogen Peroxide* / metabolism
  • Leydig Cells* / drug effects
  • Leydig Cells* / metabolism
  • Male
  • Mice
  • Monosaccharides
  • Oxidative Stress / drug effects
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Reactive Oxygen Species / metabolism
  • Sambucus / chemistry
  • Testosterone*

Substances

  • Hydrogen Peroxide
  • Plant Extracts
  • Testosterone
  • Amino Acids
  • Monosaccharides
  • Reactive Oxygen Species
  • steroidogenic acute regulatory protein
  • Phosphoproteins

Grants and funding

This research was supported by a grant from the Technology Development Program (S2778672) funded by the Korea Technology & Infor-mation Promotion Agency for SMEs, TIPA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.